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Conference Paper: The identification of sequence elements that mediate stabilization of the CHOP/Gadd153 mRNA by N-(4-hydroxyphenyl)retinamide (4HPR/fenretinide)

TitleThe identification of sequence elements that mediate stabilization of the CHOP/Gadd153 mRNA by N-(4-hydroxyphenyl)retinamide (4HPR/fenretinide)
Authors
Issue Date2007
PublisherAmerican Association for Cancer Research
Citation
The 98th AACR Annual Meeting, Los Angeles, CA, 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, p. LB-200 How to Cite?
AbstractThe CHOP, or the growth-arrest and DNA-damage-inducible gene (Gadd153) encodes a C/EBP-homologous protein that was previously shown to express in cultured cancer cells in response to the anticancer agent, N-(4-hydroxyphenyl)retinamide (4HPR or fenretinide). The 4HPR-induced expression of Gadd153 involves the stabilization of Gadd153 mRNA through a mechanism that is dependent on the production of reactive oxygen species. In this communication, we demonstrated by base-substitution and deletion analyses of the full-length Gadd153 cDNA that an adenylate-uridylate rich (AU-rich) element present in the 3’UTR of Gadd153 mRNA is essential for the mRNA-stabilization effect of 4HPR. However, a chimeric mRNA consisting of the 3’UTR of Gadd153 mRNA joined to the 3’-end of the coding sequence of green-fluorescent protein (GFP) was not stabilized. On the contrary, a similar chimeric mRNA consisting of the GFP coding sequence and a longer Gadd153 mRNA-fragment (containing the last 358 nucleotides of the Gadd153 coding sequence and the entire 3’UTR) was stabilized by 4HPR. These observations suggest that the AU-rich element in the 3’UTR of Gadd153 mRNA alone is not sufficient for 4HPR-induced mRNA stability. Examination of stability of mRNA species transcribed from various deletion and base-substituted mutants of Gadd153 cDNA revealed the presence of a 14-nucleotide sequence element (lying 39 nucleotides upstream of the last codon in the reading frame) that acted as a co-requisite sequence element for 4HPR-induced stability of Gadd153 mRNA. The deletion of sequences in between the 14-nucleotide sequence element and the AU-rich element did not affect 4HPR-induced stability of the resultant mRNA species. Our data demonstrate for the first time that the 4HPR-induced stability of Gadd153 mRNA is co-mediated by the AU-rich element and a novel sequence element of Gadd153 mRNA. Such a mechanism may be required for the sustained expression of Gadd153.
Persistent Identifierhttp://hdl.handle.net/10722/96656
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorLai, WLen_HK
dc.contributor.authorWong, NSen_HK
dc.date.accessioned2010-09-25T16:40:37Z-
dc.date.available2010-09-25T16:40:37Z-
dc.date.issued2007en_HK
dc.identifier.citationThe 98th AACR Annual Meeting, Los Angeles, CA, 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, p. LB-200-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/96656-
dc.description.abstractThe CHOP, or the growth-arrest and DNA-damage-inducible gene (Gadd153) encodes a C/EBP-homologous protein that was previously shown to express in cultured cancer cells in response to the anticancer agent, N-(4-hydroxyphenyl)retinamide (4HPR or fenretinide). The 4HPR-induced expression of Gadd153 involves the stabilization of Gadd153 mRNA through a mechanism that is dependent on the production of reactive oxygen species. In this communication, we demonstrated by base-substitution and deletion analyses of the full-length Gadd153 cDNA that an adenylate-uridylate rich (AU-rich) element present in the 3’UTR of Gadd153 mRNA is essential for the mRNA-stabilization effect of 4HPR. However, a chimeric mRNA consisting of the 3’UTR of Gadd153 mRNA joined to the 3’-end of the coding sequence of green-fluorescent protein (GFP) was not stabilized. On the contrary, a similar chimeric mRNA consisting of the GFP coding sequence and a longer Gadd153 mRNA-fragment (containing the last 358 nucleotides of the Gadd153 coding sequence and the entire 3’UTR) was stabilized by 4HPR. These observations suggest that the AU-rich element in the 3’UTR of Gadd153 mRNA alone is not sufficient for 4HPR-induced mRNA stability. Examination of stability of mRNA species transcribed from various deletion and base-substituted mutants of Gadd153 cDNA revealed the presence of a 14-nucleotide sequence element (lying 39 nucleotides upstream of the last codon in the reading frame) that acted as a co-requisite sequence element for 4HPR-induced stability of Gadd153 mRNA. The deletion of sequences in between the 14-nucleotide sequence element and the AU-rich element did not affect 4HPR-induced stability of the resultant mRNA species. Our data demonstrate for the first time that the 4HPR-induced stability of Gadd153 mRNA is co-mediated by the AU-rich element and a novel sequence element of Gadd153 mRNA. Such a mechanism may be required for the sustained expression of Gadd153.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Researchen_HK
dc.titleThe identification of sequence elements that mediate stabilization of the CHOP/Gadd153 mRNA by N-(4-hydroxyphenyl)retinamide (4HPR/fenretinide)en_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLai, WL: bennywll@hku.hken_HK
dc.identifier.emailWong, NS: nswong@hkucc.hku.hken_HK
dc.identifier.authorityWong, NS=rp00340en_HK
dc.identifier.hkuros132446en_HK

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